Two new oleanane triterpenes from Maytenus hookeri.

Two new triterpenes mayteneri A (1), mayteneri B (2), and seven known compounds (3-9) were isolated from stems of Maytenus hookeri Loes. The chemical structures of compounds 1 and 2 were established by 1D, 2D NMR, HRESIMS analysis, and calculating electronic circular dichroism (ECD). The structures of known compounds 3-9 were determined by comparison of their spectral with those reported. Compounds 4-7 showed significant inhibitory activity for NLRP3 inflammasome, with the IC50 values of 2.36-3.44 µM.

Dynamic tensile viscoelastic properties of porcine periodontal ligament.

The periodontal ligament plays a significant role in orthodontic and masticatory processes. To explicitly investigate the effects of dynamic force amplitude and frequency on the dynamic tensile properties of the periodontal ligament, in vitro tensile experiments were conducted using a dynamic mechanical analysis at various dynamic force amplitudes across a wide frequency range. Storage modulus, loss modulus, and loss factor values were measured. A Maxwell constitutive model based on modulus was established to describe the dynamic mechanical properties of the periodontal ligament. The results showed that the storage modulus ranged from 29.53 MPa to 158.24 MPa, the loss modulus ranged from 3.26 MPa to 76.16 MPa, and the loss factor values all increased with higher frequencies and higher dynamic force amplitudes. Based on the parameters obtained from the fitting results, it is evident that the short-term response has a more pronounced impact on the elastic response of the periodontal ligament than the long-term response. Increasing the dynamic force amplitude and its frequency amplified the viscous effects of the periodontal ligament and enhanced energy dissipation. The proposed constitutive model further demonstrated that the periodontal ligament acts as a viscoelastic biomaterial. These findings have implications for future research on the periodontal ligament.

Leaching behaviour of 226Ra from uranium tailings and adsorption behaviour in geotechnical medias.

The leaching process of uranium tailings is a typical water-rock interaction. The release of 226Ra from uranium tailings depends on the nuclides outside the intrinsic properties of uranium tailings on the one hand, and is influenced by the water medium on the other. In this paper, a uranium tailings repository in southern China was used as a research object, and uranium tailings at different depths were collected by drilling samples and mixed to analyze the 226Ra occurrence states. Static dissolution leaching experiments of 226Ra under different pH conditions, solid-liquid ratio conditions, and ionic strength conditions were carried out, and the adsorption and desorption behaviours of 226Ra in five representative stratigraphic media were investigated. The results show that 226Ra has a strong adsorption capacity in representative strata, with adsorption distribution coefficient Kd values ranging from 1.07E+02 to 1.29E+03 (mL/g) and desorption distribution coefficients ranging from 4.97E+02 to 2.71E+03 (mL/g), but the adsorption is reversible. The 226Ra in uranium tailings exists mainly in the residual and water-soluble states, and the release of 226Ra from uranium tailings under different conditions is mainly from the water-soluble and exchangeable state fractions. Low pH conditions, low solid-liquid ratio conditions and high ionic strength conditions are favourable to the release of 226Ra from uranium tailings, so the release of 226Ra from uranium tailings can be reduced by means of adjusting the pH in the tailings and setting up a water barrier. The results of this research have important guiding significance for the management of existing uranium tailings ponds and the control of 226Ra migration in groundwater, which is conducive to guaranteeing the long-term safety, stability and sustainability of uranium mining sites.

Precast Assembled Road Paving Technology: Progress and Prospects.

This article presents a systematic review of the most cutting-edge research on precast pavement technology for the first time. Firstly, precast pavement is divided into two categories, precast cement concrete pavement and precast carpeted flexible pavement, according to the application of precast technology in pavement engineering. Subsequently, the structural characteristics, advantages, and disadvantages of various precast pavement systems are compared and analyzed; technical problems in precast pavement systems are explained; and future development directions are identified. In addition, the text specifically mentions the great contribution of precast carpeted flexible pavement technology in reducing the harmful effects of asphalt fumes on humans and the environment. This work will promote the application of prefabrication in road engineering and provide suggestions and references for subsequent research.

Nonphytotoxic and pH-responsive ZnO-ZIF­8 loaded with honokiol as a "nanoweapon" effectively controls the soil-borne bacterial pathogen Ralstonia solanacearum.

The development of intelligently released and environmentally safe nanocarriers not only aligns with the sustainable agricultural strategy but also offers a potential solution for controlling severe soil-borne bacterial diseases. Herein, the core-shell structured nanocarrier loaded with honokiol bactericide (honokiol@ZnO-ZIF-8) was synthesized via a one-pot method for the targeted control of Ralstonia solanacearum, the causative agent of tobacco bacterial wilt disease. Results indicated that honokiol@ZnO-ZIF-8 nanoparticles induced bacterial cell membrane and DNA damage through the production of excessive reactive oxygen species (ROS), thereby reducing bacterial cell viability and ultimately leading to bacterial death. Additionally, the dissociation mechanism of the nanocarriers was elucidated for the first time through thermodynamic computational simulation. The nanocarriers dissociate primarily due to H+ attacking the N atom on imidazole, causing the rupture of the Zn-N bond under acidic conditions and at room temperature. Furthermore, honokiol@ZnO-ZIF-8 exhibited potent inhibitory effects against other prominent Solanaceae pathogenic bacteria (Pseudomonas syringae pv. tabaci), demonstrating its broad-spectrum antibacterial activity. Biosafety assessment results indicated that honokiol@ZnO-ZIF-8 exhibited non-phytotoxicity towards tobacco and tomato plants, with its predominant accumulation in the roots and no translocation to aboveground tissues within a short period. This study provides potential application value for the intelligent release of green pesticides. ENVIRONMENT IMPLICATION: The indiscriminate use of agrochemicals poses a significant threat to environmental, ecological security, and sustainable development. Slow-release pesticides offer a green and durable strategy for crop disease control. In this study, we developed a non-phytotoxic and pH-responsive honokiol@ZnO-ZIF-8 nano-bactericide based on the pathogenesis of Ralstonia solanacearum. Thermodynamic simulation revealed the dissociation mechanism of ZIF-8, with different acidity controlling the dissociation rate. This provides a theoretical basis for on-demand pesticide release while reducing residue in the. Our findings provide strong evidence for effective soil-borne bacterial disease control and on-demand pesticide release.

Electroacupuncture improves apoptosis of nucleus pulposus cells via the IL-22/JAK2-STAT3 signaling pathway in a rat model of cervical intervertebral disk degeneration.

BACKGROUND: Cervical spondylosis (CS) is a prevalent disorder that can have a major negative impact on quality of life. Traditional conservative treatment has limited efficacy, and electroacupuncture (EA) is a novel treatment option. We investigated the application and molecular mechanism of EA treatment in a rat model of cervical intervertebral disk degeneration (CIDD). METHODS: The CIDD rat model was established, following which rats in the electroacupuncture (EA) group received EA. For overexpression of IL-22 or inhibition of JAK2-STAT3 signaling, the rats were injected intraperitoneally with recombinant IL-22 protein (p-IL-22) or the JAK2-STAT3 (Janus kinase 2-signal transducer and activator of transcription protein 3) inhibitor AG490 after model establishment. Rat nucleus pulposus (NP) cells were isolated and cultured. Cell counting kit-8 and flow cytometry were used to analyze the viability and apoptosis of the NP cells. Expression of IL-22, JAK2 and STAT3 was determined using RT-qPCR. Expression of IL-22/JAK2-STAT3 pathway and apoptosis related proteins was detected by Western blotting (WB). RESULTS: EA protected the NP tissues of CIDD rats by regulating the IL-22/JAK2-STAT3 pathway. Overexpression of IL-22 significantly promoted the expression of tumor necrosis factor (TNF)-α, IL-6, IL-1ß, matrix metalloproteinase (MMP)3 and MMP13 compared with the EA group. WB demonstrated that the expression of IL-22, p-JAK2, p-STAT3, caspase-3 and Bax in NP cells of the EA group was significantly reduced and Bcl-2 elevated compared with the model group. EA regulated cytokines and MMP through activation of IL-22/JAK2-STAT3 signaling in CIDD rat NP cells. CONCLUSION: We demonstrated that EA affected apoptosis by regulating the IL-22/JAK2-STAT3 pathway in NP cells and reducing inflammatory factors in the CIDD rat model. The results extend our knowledge of the mechanisms of action underlying the effects of EA as a potential treatment approach for CS in clinical practice.

Increasing structure diversity of farnesylated chalcones by a fungal aromatic prenyltransferase.

Farnesylated chalcones were favored by researchers due to their different biological activities. However, only five naturally occurring farnesylated chalcones were described in the literature until now. Here, the farnesylation of six chalcones by the Aspergillus terreus aromatic prenyltransferase AtaPT was reported. Fourteen monofarnesylated chalcones (1F1-1F5, 2F1-2F3, 3F1, 3F2, 4F1, 4F2, 5F1, 6F1, and 6F2) and a difarnesylated product (2F3) were obtained, enriching the diversity of natural farnesylated chalcones significantly. Ten of them are C-farnesylated products, which complement O-farnesylated chalcones by chemical synthesis. Fourteen products have not been reported prior to this study. Nine of the produced compounds (1F2-1F5, 2F1-2F3, 5F1, and 6F1) exhibited inhibitory effect on α-glucosidase with IC50 values ranging from 24.08 ± 1.44 to 190.0 ± 0.28 µM. Among them, compounds 2F3 with IC50 value at 24.08 ± 1.44 µM and 1F4 with IC50 value at 30.09 ± 0.59 µM showed about 20 times stronger than the positive control acarbose with an IC50 at 536.87 ± 24.25 µM in α-glucosidase inhibitory assays.

Development and validation of a deep-learning model to predict 10-year atherosclerotic cardiovascular disease risk from retinal images using the UK Biobank and EyePACS 10K datasets.

Background: Atherosclerotic cardiovascular disease (ASCVD) is a leading cause of death globally, and early detection of high-risk individuals is essential for initiating timely interventions. The authors aimed to develop and validate a deep learning (DL) model to predict an individual's elevated 10-year ASCVD risk score based on retinal images and limited demographic data. Methods: The study used 89,894 retinal fundus images from 44,176 UK Biobank participants (96% non-Hispanic White, 5% diabetic) to train and test the DL model. The DL model was developed using retinal images plus age, race/ethnicity, and sex at birth to predict an individual's 10-year ASCVD risk score using the pooled cohort equation (PCE) as the ground truth. This model was then tested on the US EyePACS 10K dataset (5.8% non-Hispanic White, 99.9% diabetic), composed of 18,900 images from 8969 diabetic individuals. Elevated ASCVD risk was defined as a PCE score of ≥7.5%. Results: In the UK Biobank internal validation dataset, the DL model achieved an area under the receiver operating characteristic curve of 0.89, sensitivity 84%, and specificity 90%, for detecting individuals with elevated ASCVD risk scores. In the EyePACS 10K and with the addition of a regression-derived diabetes modifier, it achieved sensitivity 94%, specificity 72%, mean error -0.2%, and mean absolute error 3.1%. Conclusion: This study demonstrates that DL models using retinal images can provide an additional approach to estimating ASCVD risk, as well as the value of applying DL models to different external datasets and opportunities about ASCVD risk assessment in patients living with diabetes.

Recent progress and outlooks in rhodamine-based fluorescent probes for detection and imaging of reactive oxygen, nitrogen, and sulfur species.

Reactive oxygen species (ROS), reactive nitrogen species (RNS), and reactive sulfur species (RSS) serve as vital mediators essential for preserving intracellular redox homeostasis within the human body, thereby possessing significant implications across physiological and pathological domains. Nevertheless, deviations from normal levels of ROS, RNS, and RSS disturb redox homeostasis, leading to detrimental consequences that compromise bodily integrity. This disruption is closely linked to the onset of various human diseases, thereby posing a substantial threat to human health and survival. Small-molecule fluorescent probes exhibit considerable potential as analytical instruments for the monitoring of ROS, RNS, and RSS due to their exceptional sensitivity and selectivity, operational simplicity, non-invasiveness, localization capabilities, and ability to facilitate in situ optical signal generation for real-time dynamic analyte monitoring. Due to their distinctive transition from their spirocyclic form (non-fluorescent) to their ring-opened form (fluorescent), along with their exceptional light stability, broad wavelength range, high fluorescence quantum yield, and high extinction coefficient, rhodamine fluorophores have been extensively employed in the development of fluorescent probes. This review primarily concentrates on the investigation of fluorescent probes utilizing rhodamine dyes for ROS, RNS, and RSS detection from the perspective of different response groups since 2016. The scope of this review encompasses the design of probe structures, elucidation of response mechanisms, and exploration of biological applications.

Evaluation of novel promoters for vascular tissue-specific gene expression in Populus.

Due to the extended generation cycle of trees, the breeding process for forest trees tends to be time-consuming. Genetic engineering has emerged as a viable approach to expedite the genetic breeding of forest trees. However, current genetic engineering techniques employed in forest trees often utilize continuous expression promoters such as CaMV 35S, which may result in unintended consequences by introducing genes into non-target tissues. Therefore, it is imperative to develop specific promoters for forest trees to facilitate targeted and precise design and breeding. In this study, we utilized single-cell RNA-Seq data and co-expression network analysis during wood formation to identify three vascular tissue-specific genes in poplar, PP2-A10, PXY, and VNS07, which are expressed in the phloem, cambium/expanding xylem, and mature xylem, respectively. Subsequently, we cloned the promoters of these three genes from '84K' poplar and constructed them into a vector containing the eyGFPuv visual selection marker, along with the 35S mini enhancer to drive GUS gene expression. Transgenic poplars expressing the ProPagPP2-A10::GUS, ProPagPXY::GUS, and ProPagVNS07::GUS constructs were obtained. To further elucidate the tissue specificity of these promoters, we employed qPCR, histochemical staining, and GUS enzyme activity. Our findings not only establish a solid foundation for the future utilization of these promoters to precisely express of specific functional genes in stems but also provide a novel perspective for the modular breeding of forest trees.

Chronic cypermethrin induced toxicity and molecular fate assessment within common carp (Cyprinus carpio) using multiple biomarkers approach and its novel therapeutic detoxification.

Cypermethrin (CYP) is a chemical of emerging concern which has persistent and bioaccumulating impacts as it can be found extensively in freshwater ecosystem and agricultural products. It has exposure risk and toxic effects over human edible fish, as common carp. Four groups were designed for toxicity assessment and detoxification approach: control group (CL), CYP exposure group (CYP), CYP + 10% M. oleifera leaves and 10% M. oleifera seeds (CMO group), 10% M. oleifera leaves and 10% M. oleifera seeds (MO group). Trial period was forty days during which cohort of 240 fish in CYP and CMO group was exposed to 1/5 of 96h LC50 of CYP (0.1612 µg/L). CYP-exposed carp exhibited lower growth parameters, but carp fed with 10% M. oleifera seeds and leaves showed significant improvement in growth rate (SGR, RGR) and weight gain (WG) as compared to the control group. CYP exposure negatively affected haemato-biochemical parameters. Moreover, CYP exposure also led to oxidative stress, damaged immunological parameters, genotoxicity and histopathological damage in liver and intestinal cells. Whereas, M. oleifera supplementation has ameliorated these conditions. Thereby, supplementation with M. oleifera is potential and novel therapeutic detoxication approach for common carp and human health against persistent and bioaccumulating emerging chemicals.

p-Toluenesulfonic Acid Modified Two-Dimensional ZrSe2 as a Hole Transport Layer for High-Performance Organic Solar Cells.

Two-dimensional (2D) materials have attracted attention due to their excellent optoelectronic properties, but their applications are limited by their defects and vacancies. Surface modification is an effective method to restore their performance. Here, ZrSe2 is modified with conductive polymer p-toluenesulfonic acid (PTSA). It is found that PTSA can obtain electrons of ZrSe2 through the combination of -SO3H and ZrSe2, thus forming interfacial dipoles, which improve the work function of ZrSe2. In addition, -OH in PTSA can effectively fill the Se vacancy in ZrSe2 to form P-type doping, thereby improving its conductivity. ZrSe2 modified by the PTSA material is first used as a hole transport layer (HTL) in organic solar cells (OSCs). The efficiency of OSCs based on the PBDB-T:ITIC and PM6:L8-BO binary active layer with ZrSe2:PTSA as the novel HTL reaches 10.66 and 18.14%, which are obviously higher than the efficiency of OSCs with pure ZrSe2 as the HTL (8.48 and 15.64%). More interestingly, the stability of the device with ZrSe2:PTSA as HTL is significantly better than that of PEDOT:PSS. This study shows that the modification of the organic material can effectively improve the photoelectric performance of ZrSe2 and explores the physical mechanism of the interaction between the organic modifier and 2D materials.

UroAngel: a single-kidney function prediction system based on computed tomography urography using deep learning.

BACKGROUND: Accurate estimation of the glomerular filtration rate (GFR) is clinically crucial for determining the status of obstruction, developing treatment strategies, and predicting prognosis in obstructive nephropathy (ON). We aimed to develop a deep learning-based system, named UroAngel, for non-invasive and convenient prediction of single-kidney function level. METHODS: We retrospectively collected computed tomography urography (CTU) images and emission computed tomography diagnostic reports of 520 ON patients. A 3D U-Net model was used to segment the renal parenchyma, and a logistic regression multi-classification model was used to predict renal function level. We compared the predictive performance of UroAngel with the Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations, and two expert radiologists in an additional 40 ON patients to validate clinical effectiveness. RESULTS: UroAngel based on 3D U-Net convolutional neural network could segment the renal cortex accurately, with a Dice similarity coefficient of 0.861. Using the segmented renal cortex to predict renal function stage had high performance with an accuracy of 0.918, outperforming MDRD and CKD-EPI and two radiologists. CONCLUSIONS: We proposed an automated 3D U-Net-based analysis system for direct prediction of single-kidney function stage from CTU images. UroAngel could accurately predict single-kidney function in ON patients, providing a novel, reliable, convenient, and non-invasive method.

Comparison of the specific energies of sinusoidal VCS cutter rings and CCS cutter rings in breaking rock-like materials based on the FEM.

Disc cutters are essential for full-section hard-rock tunnel boring machines. The performance of these devices directly affects tunnel engineering costs and duration. This paper proposes a sinusoidal variable cross-section (VCS) cutter ring and design method and establishes a digital model. Rock-like materials are simulated with a finite element model, and the model validity is verified via rock simulation mechanics tests. A disc cutter rolling rock simulation model for a linear cutting machine is also established, and simulation tests are performed for single- and three-cutter rolling using sinusoidal VCSs and constant cross-section (CCS) cutter models, respectively. The stress and energy changes for the cutters and rock-like material damage area were compared via simulation, confirming that some sinusoidal VCS cutter rings do less work on rock-like materials and cause larger crushing areas under the same engineering parameters; therefore, these cutter rings have smaller specific energies. The sinusoidal VCS cutter ring performance is 7% greater than that of CCS on average under single-cutter simulation, and the intermediate cutter performance of the intermediate cutter is 9% greater than that of CCS on average under three-cutter simulation. Thus, sinusoidal VCS cutter rings offer improved rock damage performance, and further research and application of this technology will improve the working efficiency of tunnel boring machines.

Using computed tomogram atrial myocardial thickness maps in high-power short-duration radiofrequency pulmonary vein isolation: UTMOST AF.

Background: High-power short-duration (HPSD) ablation creates wide, shallow lesions using radiofrequency (RF) heating. It is uncertain if adjusting RF energy based on atrial wall thickness provides extra benefits. We studied the safety and effectiveness of tailored HPSD energy based on left atrial (LA) wall thickness (LAWT) for circumferential pulmonary vein isolation (CPVI) in patients with paroxysmal atrial fibrillation (PAF). Methods: We enrolled 212 patients (68.4% male, mean age: 59.5 ± 11.0 years) and randomly assigned them to two groups: LAWT-guided CPVI (WT, n = 108) and conventional CPVI (control, n = 104). Both groups used an open irrigated-tip deflectable catheter to apply 50 W for 10 s to the posterior LA, while controls used 60 W for 15 s on other LA regions. RF delivery time in WT was titrated (15 s at LAWT > 2.1 mm, 13 s at 1.4-2.1 mm, and 11 s at <1.4 mm) according to the computed tomogram-myocardial thickness color map. Results: After a mean follow-up of 13.4 ± 7.0 months, the WT and control groups showed no significant difference regarding clinical recurrence rate (13.9% vs. 5.8%, respectively; p = .061) and major complication rate (4.6% vs. 3.8%, respectively; p > .999). The total procedure time, cardioversion rate, and post-procedural AAD prescription rates did not significantly differ between the groups. Conclusions: The LAWT-guided energy titration strategy did not result in improved procedural safety and efficacy compared to the conventional 50-60 W-HPSD CPVI in patients with PAF.

Beyond the ß-amino alcohols framework: identification of novel ß-hydroxy pyridinium salt-decorated pterostilbene derivatives as bacterial virulence factor inhibitors.

BACKGROUND: Bacterial virulence factors are involved in various biological processes and mediate persistent bacterial infections. Focusing on virulence factors of phytopathogenic bacteria is an attractive strategy and crucial direction in pesticide discovery to prevent invasive and persistent bacterial infection. Hence, discovery and development of novel agrochemicals with high activity, low-risk, and potent anti-virulence is urgently needed to control plant bacterial diseases. RESULTS: A series of novel ß-hydroxy pyridinium cation decorated pterostilbene derivatives were prepared and their antibacterial activities against Xanthomonas oryzae pv. oryzae (Xoo) were systematacially assessed. Among these pterostilbene derivatives, compound 4S exhibited the best antibacterial activity against Xoo in vitro, with an half maximal effective concentration (EC50) value of 0.28 µg mL-1. A series of biochemical assays including scanning electron microscopy, crystal violet staining, and analysis of biofilm formation, swimming motility, and related virulence factor gene expression levels demonstrated that compound 4S could function as a new anti-virulence factor inhibitor by interfering with the bacterial infection process. Furthermore, the pot experiments provided convinced evidence that compound 4S had the high control efficacy (curative activity: 71.4%, protective activity: 72.6%), and could be used to effectively manage rice bacterial leaf blight in vivo. CONCLUSION: Compounds 4S is an attractive virulence factor inhibitor with potential for application in treating plant bacterial diseases by suppressing production of several virulence factors. © 2024 Society of Chemical Industry.

Adsorption-desorption of 241Am(â ¢) on montmorillonite colloids and quartz sand: Effects of pH, ionic strength, colloid concentration and grain size.

Clay colloids in the subsurface environment have a strong adsorption capacity for radionuclides, and the mobile colloids will carry the nuclides for migration, which would promote the movability of radionuclides in the groundwater environment and pose a threat to the ecosphere. The investigations of the adsorption/desorption behaviors of radionuclides in colloids and porous media are significant for the evaluation of the geological disposal of radioactive wastes. To illustrate the adsorption/desorption behaviors of 241Am(Ⅲ) in Na-montmorillonite colloid and/or quartz sand systems at different pH (5, 7 and 9), ionic strengths (0, 0.1 and 5 mM), colloid concentrations (300 and 900 mg/L), nuclide concentrations (500, 800, 1100 and 1400 Bq/mL) and grain sizes (40 and 60 mesh), a series of batch sorption-desorption experiments were conducted. Combining the analysis of the physical and chemical properties of Na-montmorillonite with the Freundlich model, the influencing mechanism of different controlling factors is discussed. The experimental results show that the adsorption/desorption behaviors of 241Am(Ⅲ) in Na-montmorillonite colloid and/or quartz sand strongly are influenced by the pH value and ionic strength of a solution, the colloid concentration as well as quartz sand grain size. The adsorption and desorption isotherms within all the experimental conditions could be well-fitted by the Freundlich model and the correlation coefficients (R2) are bigger than 0.9. With the increase in pH, the adsorption partition coefficient (Kd) at 241Am(Ⅲ)-Na-montmorillonite colloid two-phase system and 241Am(Ⅲ)-Na-montmorillonite colloid-quartz sand three-phase system presents a trend which increases firstly followed by decreasing, due to the changes in the morphology of Am with pH. The Kd of 241Am(Ⅲ) adsorption on montmorillonite colloid and quartz sand decreases with increasing in ionic strength, which is mainly attributed to the competitive adsorption, surface complexation and the reduction of surface zeta potential. Additionally, the Kd increases with increasing colloid concentrations because of the increase in adsorption sites. When the mean grain diameter changes from 0.45 to 0.3 mm, the adsorption variation trends of 241Am(Ⅲ) remain basically unchanged. The research results obtained in this work are meaningful and helpful in understanding the migration behaviors of radionuclides in the underground environment.

Unraveling the immunological landscape in acute pancreatitis progression to sepsis: insights from a Mendelian randomization study on immune cell traits.

Background: Acute pancreatitis (AP) is a severe digestive system disorder with a significant risk of progressing to sepsis, a major cause of mortality. Unraveling the immunological pathways in AP is essential for developing effective treatments, particularly understanding the role of specific immune cell traits in this progression. Methods: Employing a bidirectional two-sample Mendelian Randomization (MR) approach, this study first examined the causal relationship between AP and 731 immune cell traits to identify those significantly associated with AP. Subsequently, we explored the causal associations between 731 immune cell traits and sepsis. The analysis utilized extensive genome-wide association studies (GWAS) summary datasets, with a focus on identifying common immune cell traits with statistically significant causal associations between AP and sepsis. Results: Our investigation identified 44 immune cell traits unidirectionally associated with AP and 36 traits unidirectionally associated with sepsis. Among these, CD127 on CD28+ CD45RA- CD8+ T cells emerged as a common mediator, accounting for 5.296% of the increased risk of sepsis in AP patients. This finding highlights the significant role of specific memory CD8+ T cells in the pathophysiology of AP and its progression to sepsis. Conclusion: This study elucidates the critical role of specific immune cell traits, particularly CD127hi memory CD8+ T cells, in the progression of AP to sepsis. Our findings provide a foundation for future research into targeted immune-modulatory therapies, potentially improving patient outcomes in AP-related sepsis and offering new insights into the complex immunological dynamics of this condition.

Dietary sodium acetate and sodium butyrate improve high-carbohydrate diet utilization by regulating gut microbiota, liver lipid metabolism, oxidative stress, and inflammation in largemouth bass (Micropterus salmoides).

BACKGROUND: Adequate level of carbohydrates in aquafeeds help to conserve protein and reduce cost. However, studies have indicated that high-carbohydrate (HC) diet disrupt the homeostasis of the gut-liver axis in largemouth bass, resulting in decreased intestinal acetate and butyrate level. METHOD: Herein, we had concepted a set of feeding experiment to assess the effects of dietary sodium acetate (SA) and sodium butyrate (SB) on liver health and the intestinal microbiota in largemouth bass fed an HC diet. The experimental design comprised 5 isonitrogenous and isolipidic diets, including LC (9% starch), HC (18% starch), HCSA (18% starch; 2 g/kg SA), HCSB (18% starch; 2 g/kg SB), and HCSASB (18% starch; 1 g/kg SA + 1 g/kg SB). Juvenile largemouth bass with an initial body weight of 7.00 ± 0.20 g were fed on these diets for 56 d. RESULTS: We found that dietary SA and SB reduced hepatic triglyceride accumulation by activating autophagy (ATG101, LC3B and TFEB), promoting lipolysis (CPT1α, HSL and AMPKα), and inhibiting adipogenesis (FAS, ACCA, SCD1 and PPARγ). In addition, SA and SB decreased oxidative stress in the liver (CAT, GPX1α and SOD1) by activating the Keap1-Nrf2 pathway. Meanwhile, SA and SB alleviated HC-induced inflammation by downregulating the expression of pro-inflammatory factors (IL-1ß, COX2 and Hepcidin1) through the NF-κB pathway. Importantly, SA and SB increased the abundance of bacteria that produced acetic acid and butyrate (Clostridium_sensu_stricto_1). Combined with the KEGG analysis, the results showed that SA and SB enriched carbohydrate metabolism and amino acid metabolism pathways, thereby improving the utilization of carbohydrates. Pearson correlation analysis indicated that growth performance was closely related to hepatic lipid deposition, autophagy, antioxidant capacity, inflammation, and intestinal microbial composition. CONCLUSIONS: In conclusion, dietary SA and SB can reduce hepatic lipid deposition; and alleviate oxidative stress and inflammation in largemouth bass fed on HC diet. These beneficial effects may be due to the altered composition of the gut microbiota caused by SA and SB. The improvement effects of SB were stronger than those associated with SA.